• Port-a-Patch

    世界最小パッチクランプセットアップ
  • Port-a-Patch

    誰でもデータ取得 - 教育ツールとして最適
  • Port-a-Patch

    細胞, オルガネラ, 脂質二分子膜
  • Port-a-Patch

    世界で最も歴史あるプレーナー式パッチクランプ装置
  • Port-a-Patch

    細胞内灌流実験に最適

2013 - Crystal structure and functional mechanism of a human antimicrobial membrane channel

icon pap   Port-a-Patch publication in Proceedings of the National Academy of Sciences of the United States of America (2013)

Authors: 
Songa C., Weichbrodt C., Salnikov E.S., Dynowski M.,Forsberg B.O., Bechinger B., Steinem C., de Groot B.L., Zachariae U. and Zeth K.

 

Journal: 
Proc Natl Acad Sci USA (2013) 110(12):4586–4591


Abstract: 

Multicellular organisms fight bacterial and fungal infections by producing peptide-derived broad-spectrum antibiotics. These host-defense peptides compromise the integrity of microbial cell membranes and thus evade pathways by which bacteria develop rapid antibiotic resistance. Although more than 1,700 host-defense peptides have been identified, the structural and mechanistic basis of their action remains speculative. This impedes the desired rational development of these agents into next-generation antibiotics. We present the X-ray crystal structure as well as solid-state NMR spectroscopy, electrophysiology, and MD simulations of human dermcidin in membranes that reveal the antibiotic mechanism of this major human antimicrobial, found to suppress Staphylococcus aureus growth on the epidermal surface. Dermcidin forms an architecture of high-conductance transmembrane channels, composed of zinc-connected trimers of antiparallel helix pairs. Molecular dynamics simulations elucidate the unusual membrane permeation pathway for ions and show adjustment of the pore to various membranes. Our study unravels the comprehensive mechanism for the membrane-disruptive action of this mammalian host-defense peptide at atomistic level. The results may form a foundation for the structure-based design of peptide antibiotics.


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